M protein, a fibrillar molecule on the surface of the group A streptococcus, confers on the organism the ability to resist attack by human phagocytic cell. This characteristic suggests that the M protein is one of the major virulence factors for this bacterium. While anti-M protein antibodies protect against subsequent streptococcal infection, this protection is specific for a particular serotype of M protein. To approach the question of broad protection form infection by group A streptococci, an understanding of the M protein on a genetic, and a structural and functional level is important. In our previous work, we cloned the M protein in E. coli and determined its complete DNA sequence. This suggested genetic mechanisms that give rise to antigentically varied M protein molecules. In our future work, we propose to continue to use genetic and immunological techniques to further our understanding of the molecule. We wish to test our models for the genetic basis of antigenic variation of M proteins, to examine the molecular characteristics of the molecule needed for attachment to the streptococcal cell wall, to determine in molecular detail the relationship of the structure of this molecule to its function, and to define the structure of epitopes recognized by opsonic antibodies.